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Endotoxin enhances the fibrinolytic activity of monocytes incorporated in a fibrin clot
Critical Care volume 9, Article number: P155 (2005)
Background
In sepsis, one of the most important problems is the modification of the hemostasis balance with activation of the coagulation. This is due, in part, to increased expression of tissue factor at the monocyte surface [1]. In these patients, we also observe a systemic hypofibrinolysis [2]. However, it is known that leukocytes have a profibrinolytic potential [3].
Aim
To explore the role of monocytes in the fibrinolytic balance.
Materials and methods
THP-1, a monocytoïd cell line, was challenged or not with 10 μg/ml lipopolysaccharide during 4 hours, before being introduced in an euglobulin clot lysis time assay, measured by a new semi-automatic method [4]. Resting cells were introduced in the assay at concentrations ranging from 0.25 × 106 cells/ml to 106 cells/ml and stimulated cells at the concentration of 106 cells/ml. Control without cells is the baseline. Statistics used analysis of variance.
Results
First, we observed a gradual diminution of lysis time with resting cells, from 12% to 25% of the baseline, according to the concentration of cells (n = 6; P < 0.001). Then, when we added stimulated THP-1, we observed a greater diminution of lysis time: 31% of the baseline (n = 8; P < 0.001 from the baseline and P < 0.05 from resting cells).
Conclusion
Monocytes play a role in the fibrinolytic balance and this role is enhanced when they are activated by lipopolysaccharide, like in sepsis. In the future, we will have to investigate why monoyctes are responsible for such an antagonism, stimulating coagulation and fibrinolytic processes, at the same time.
References
Gregory SA, Morrissey JH, Edgington TS: Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol. Cell Biol 1989, 9: 2752-2755.
van Deventer SJH, Büller HR, Ten Cate JW, Aarden LA, Hack CE, Sturk A: Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood 1990, 76: 2520-2526.
Rulot H: Intervention des leucocytes dans l'autolyse de la fibrine. Arch Int Physiol 1904, 1: 152-158.
Zouaoui Boudjeltia K, Cauchie P, Remacle C, Guillaume M, Brohee D, Hubert JL, Vanhaeverbeek M: A new device for measurement of fibrin clot lysis: application to the euglobulin clot lysis time. BMC Biotechnol 2002, 2: 8. 10.1186/1472-6750-2-8
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Grosjean, A., Zouaoui Boudjeltia, K., Piagnerelli, M. et al. Endotoxin enhances the fibrinolytic activity of monocytes incorporated in a fibrin clot. Crit Care 9 (Suppl 1), P155 (2005). https://doi.org/10.1186/cc3218
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DOI: https://doi.org/10.1186/cc3218